Acetylcholine receptor pathway in lung cancer: New twists to an old story

Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine(ACh) or other biologic compounds including nicotine. n ACh Rs have been found on lung cancer cells, underscoring the idea that the non-neuronal n ACh R pathway has important implications for lung cancer. Several studies focusing on the treatment with n ACh R antagonists with improved selectivity might trigger novel strategies for the intervention and prevention of lung cancer. Here we review the genetic risk factors for lung cancer in the n ACh R gene cluster, the roles of nicotine receptors, and the molecular mechanisms of acetylcholine receptor pathways to lead to more opportunities for intervention and prevention of lung cancer.